Patricia Dauer

INTRODUCTION: Black women are 41% more likely to die from breast cancer compared to White women yet remain underrepresented in clinical trials and population studies. We have previously shown a higher proportion of Black women with HR+HER2- tumors further classify as Basal-Type compared with White women, using BluePrint molecular subtyping. Other studies have demonstrated higher 3-year recurrence rates in patients with BluePrint Basal-Type tumors compared to Luminal-Type. To determine whether the increased frequency of HR+/Basal-Type tumors impacts long-term outcomes in this cohort, we compared 3-year outcomes with BluePrint and the risk of distant recurrence signature, MammaPrint (MP), between Black and White women with HR+HER2- breast cancer. We also evaluated the association of MP and BluePrint with 10-year outcomes in a subset of Black women. METHODS: This study …

Objective: The present systematic review aimed to provide an overview of training load (TL), along with their responses, monitoring during training sessions in highly trained and elite adult women soccer players.Data source: Electronic databases searches (PubMed, Scopus, Web of Science and Ebsco) for relevant studies published in peer-reviewed journals were conducted, and eligibility criteria were based on the PICOS model in accordance with PRISMA guidelines.Study selection: Studies were considered as follows:(a) highly trained and elite adult (> 18 years) women's soccer players;(b) continuous (minimum1-week duration) TL monitoring in the context of the team routine;(c) TL collected from entire training session. Methodological qualitative assessments and risk of bias criteria were used for judging the studies.Data extraction: A total of 1,163 studies were identified, and 16 were included. The selected studies were fully screened to extract the population characteristics; the number of players; a type of study design; region where the study was performed; the main findings.Data synthesis: Accumulated external TL (ETL) during the pre-season was positively correlated to enhanced adaptations in intermittent exercise capacity. Daily ETL was negatively correlated to next-day self-reported fatigue and muscle soreness. Daily internal TL (ITL) was negatively correlated to postsession sleep duration and sleep efficiency. One study showed that higher accumulated player load and total distance were associated with injury.

ASO Visual Abstract: The Predictive Utility of MammaPrint and BluePrint in Identifying Patients with Locally Advanced Breast Cancer Who are Most Likely to have Nodal Downstaging and a Pathologic Complete Response After Neoadjuvant Chemotherapy ASO Visual Abstract: The Predictive Utility of MammaPrint and BluePrint in Identifying Patients with Locally Advanced Breast Cancer Who are Most Likely to have Nodal Downstaging and a Pathologic Complete Response After Neoadjuvant Chemotherapy Ann Surg Oncol. 2024 Jan;31(1):393-394. doi: 10.1245/s10434-023-14317-2. Authors Peter Blumencranz 1 , Mehran Habibi 2 , Steve Shivers 3 , Geza Acs 4 , Lisa E Blumencranz 5 , Erin B Yoder 5 , Bastiaan van der Baan 6 , Andrea R Menicucci 5 , Patricia Dauer 5 , William Audeh 7 , Charles E Cox 3 Affiliations 1 BayCare Oncology, Clearwater, FL, USA. 2 Johns Hopkins University, Baltimore, MD, USA. 3 …

BackgroundNeoadjuvant chemotherapy (NCT) increases the feasibility of surgical resection by downstaging large primary breast tumors and nodal involvement, which may result in surgical de-escalation and improved outcomes. This subanalysis from the Multi-Institutional Neo-adjuvant Therapy MammaPrint Project I (MINT) trial evaluated the association between MammaPrint and BluePrint with nodal downstaging.Patients and MethodsThe prospective MINT trial (NCT01501487) enrolled 387 patients between 2011 and 2016 aged ≥ 18 years with invasive breast cancer (T2–T4). This subanalysis includes 146 patients with stage II–III, lymph node positive, who received NCT. MammaPrint stratifies tumors as having a Low Risk or High Risk of distant metastasis. Together with MammaPrint, BluePrint genomically (g) categorizes tumors as gLuminal A, gLuminal B, gHER2, or gBasal.ResultsOverall, 45.2% (n = 66/146 …

Preeclampsia (PE) is a serious hypertensive complication of pregnancy and is a leading cause of maternal death and major contributor to maternal and perinatal morbidity, including establishment of long‐term complications. The continued prevalence of PE stresses the need for identification of novel treatments which can target prohypertensive factors implicated in the disease pathophysiology, such as soluble fms‐like tyrosine kinase 1 (sFlt‐1). We set out to identify novel compounds to reduce placental sFlt‐1 and determine whether this occurs via hypoxia‐inducible factor (HIF)‐1α inhibition. We utilized a commercially available library of natural compounds to assess their ability to reduce sFlt‐1 release from primary human placental cytotrophoblast cells (CTBs). Human placental explants from normotensive (NT) and preeclamptic (PE) pregnancies were treated with varying concentrations of luteolin. Protein and …

In this study, BluePrint consistently further stratified heterogeneous cHER2 tumors, independent of race. Unlike our observations in HR+ HER2-tumors, these data suggest that race may not influence the underlying biology of cHER2 tumors. The rate of further classification with BluePrint among cHER2 tumors was comparable to NBRST8 and APHINITY9, which demonstrated that patients with gHER2 tumors benefitted most from dual HER2-targeted therapy.The pCR rates to neoadjuvant therapy appear lower in Black patients compared to White patients with gHER2 tumors. These data are limited by sample size and should be confirmed with a larger cohort; however, they are in line with a recent study showing Black women with cHER2 tumors had lower pCR rates than White women10.

Background Preeclampsia is a disease with far-reaching consequences that extend beyond the immediate postpartum period and have a significant impact later in life. Preeclampsia exerts an effect on most organ systems in the body. These sequelae are mediated in part by the incompletely elucidated pathophysiology of preeclampsia and the associated vascular changes. Content Current research focuses on unraveling the pathophysiology of preeclampsia with the goal of implementing accurate screening and treatment modalities based on disease development and progression. Preeclampsia causes significant short- and long-term maternal morbidity and mortality, not only in the cardiovascular system but also in other organ systems throughout the body. This impact persists beyond pregnancy and the immediate postpartum period. Summary The goal of this review is to discuss the current understanding of the pathophysiology of preeclampsia as it relates to the adverse health consequences in patients impacted by this disease, along with a brief discussion of ways to improve overall outcomes.

BACKGROUND: Immune checkpoint inhibitors in combination with chemotherapy have demonstrated an improvement of pathologic complete response (pCR) in patients with HR-HER2- and MammaPrint (MP) High Risk, HR+HER2- tumors in the I-SPY2 TRIAL. However, not all patients benefit from immune checkpoint blockade and these new agents come with additional financial burden and significant long-lasting side effects such as adrenal insufficiency. Thus, it is imperative to better understand who benefits. Response Predictive Subtypes (RPS) were developed in the I-SPY2 TRIAL using pre-treatment expression data from 987 MP High Risk patients; 39% of HR+HER2- tumors and 63% of HR-HER2- tumors were identified as immune sensitive. In I-SPY2.2, RPS tumor classification uses ImPrint, a 53-gene signature that has been independently validated to predict the likelihood of a pCR with PD1-PDL1 …

BACKGROUND: Neoadjuvant Endocrine Therapy (NET) is seldom used in breast cancer management except in patients with several comorbidities or in elderly patients in which chemotherapy is not an option. Clinical response with NET is not typically achieved until after several months of treatment. In the NET setting, reduction of Ki67 (< 10%) after 2-4 weeks has been used as a predictor of positive response, but studies such as ALTERNATE have questioned this association. It remains uncertain whether a single gene or protein can adequately predict outcomes or inform how NET alters a variety of cancer genes and global tumor biology. This study evaluated the effect of short-term NET on the tumor genomics of patients with early-stage breast cancer (EBC) by comparing whole transcriptome gene expression changes in matched pre- and post-NET tumor samples. METHODS: In this single-institution FLEX …

BackgroundAs more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET.Methods1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's …

PURPOSEThe prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer.METHODSStandard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years.RESULTSAmong clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type …

585Background: The use of neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer (EBC) increases the opportunity for genomic testing which can help predict treatment response and optimize outcomes. MammaPrint (MP) classifies tumors as having a Low Risk (LR) or High Risk (HR) of distant recurrence. MP with BluePrint (BP), a molecular subtyping assay, categorize tumors as Luminal A (MP LR), Luminal B (MP HR), HER2, or Basal-Type. Our recent analysis comparing matched pre- and post-NAC tumors found 25% of pre-NAC Luminal B tumors changed to Luminal A post-NAC, which corresponded with improved 5-year outcomes compared with patients who remained Luminal B. Here, we report differential gene expression (DGE) and pathway analyses in these matched tumors that may distinguish the different responses. Methods: Among the patients with EBC who received NAC at …

517Background: Breast cancer is the leading cause of cancer-associated death among Black women, and they are 41% more likely to die from breast cancer compared to White women. Few studies have evaluated if tumor biology differences contribute to this disparity in outcomes. Similar to triple negative breast cancer (TNBC), hormone receptor-positive (HR+) tumors classified as Basal-Type with BluePrint genomic analysis (HR+/Basal) are more aggressive, higher grade, are over-represented among young Black women and have worse clinical outcomes. TNBC is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the over-representation and worse outcomes among Black women with HR+/Basal tumors, we compared differentially expressed genes (DEGs) by race and subtype. Methods: This study includes 2657 women with Stage …

Background and Objectives With increased neoadjuvant therapy recommendations for early‐stage breast cancer patients due to the COVID‐19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. Methods Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. Results We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance …

FLEX Study: EBC patients enrolled in the FLEX study (NCT03053193) undergo standard of care MammaPrint (MP) and BluePrint (BP) tests, and consent to clinically annotated whole transcriptome data collection. MP categorizes tumors as High Risk (HR) or Low Risk (LR) of recurrence. Together, MP and BP classify the molecular subtype of tumors as Luminal A-Type, Luminal B-Type, HER2-Type, or Basal-Type.

Introduction: Young women with estrogen receptor (ER)-positive early-stage breast cancer (EBC) frequently present with larger, higher-grade, more aggressive tumors, with lower ER expression than older women. Post-hoc analyses within the MINDACT and TAILORx cohorts reported that women aged 40-50 with ER+ EBC exhibited a chemotherapy benefit independent of genomic risk compared to women aged > 50, possibly due to chemotherapy-induced ovarian suppression (CIOS). However, women < 40 years, who seldom develop CIOS, are under-represented in clinical trials. Therefore, it is important to distinguish the tumor biological profile within this younger age group. To understand the biological basis underlying why younger women have poorer outcomes than older women, this study aimed to identify genes that distinguish tumors in younger women from older women. Methods: EBC patients enrolled in …

Patient Cohort: MP classifies tumors as having High Risk (HR) or Low Risk (LR) of distant recurrence. MP combined with BP define tumor subtype as either Luminal A-Type (MP LR; 56.8%), Luminal B-Type (MP HR; 36.4%), HER2-Type (1.5%), or Basal-Type (5.3%). Our primary comparison was between pT1pN1+ and pT2-3pN0 tumors, with pT1pN0 and pT2-3pN1+ as controls (Table 1).Gene Expression Analysis: R package ‘limma’was used for quantile normalization and differential gene expression analyses. Differentially expressed genes (DEGs) with a false discovery rate< 0.05 and log2 fold change> 0.5 were considered significant for this exploratory analysis. Gene set enrichment analysis (GSEA) was performed using the Hallmark gene sets (MSigDB).